Romosozumab promotes bone formation and reduces bone resorption through its novel mechanism of action, which blocks the actions of sclerostin.

In an effort to provide the most up-to-date guidance on treatment of postmenopausal osteoporosis, the Endocrine Society has issued an update to the organization’s 2019 clinical practice guideline on pharmacologic management of osteoporosis.1 The update incorporates information about romosozumab, a sclerostin-targeting monoclonal antibody that was approved by the United States Food and Drug Administration in April 2019, a month after the guideline was originally published.2

Romosozumab has demonstrated efficacy in promoting bone formation in addition to reducing bone resorption through sclerostin inhibition, as opposed to directly acting on the parathyroid hormone type 1 receptor like other anabolic agents. Based on supporting clinical trial evidence, the Endocrine Society guideline now recommends romosozumab as first-line therapy in postmenopausal women with severe osteoporosis.1

The updated guideline recommendations include1:

To reduce risk for vertebral, hip, and nonvertebral fractures, treatment with once-monthly romosozumab (210 mg) is recommended for up to 1 year in postmenopausal women with osteoporosis at very high risk for fracture, including those with low bone density T-scores (<-2.5) or with multiple vertebral fractures

After completing a course of romosozumab, it is recommended that patients receive treatment with antiresorptive therapies to maintain gains in bone density and reductions in fracture risk

These new recommendations were supported by 2 large phase 3 trials: the Fracture Study in Postmenopausal Women with Osteoporosis (FRAME; ClinicalTrials.gov Identifier: NCT01575834) and Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH; ClinicalTrials.gov Identifier: NCT01631214).1

Of note, romosozumab carries a boxed warning in its product label that cautions against use in patients at increased risk for myocardial infarction, stroke, and cardiovascular death. Although the overall number of these events was small in clinical trials, the Endocrine Society guideline recommends against use of romosozumab in women at high risk for major adverse cardiovascular events pending further studies on the medication’s cardiovascular safety.1

“Romosozumab offers promising results for postmenopausal women with severe osteoporosis or who have a history of fractures,” said Clifford J. Rosen, MD, chair of the guideline writing committee and director of the Center for Clinical and Translational Research at the Maine Medical Center Research Institute in Scarborough, Maine, in a press release.2 “It does, however, come with a risk of heart disease, so clinicians need to be careful when selecting patients for this therapy.”